Ethylenediaminetriacetic acid (ED3A) or its salts (such as ED3ANa.sub.3) has applications in the field of chelating chemistry, and may be used as a starting material in the preparation of strong chelating polymers, oil soluble chelants, surfactants and others. Conventional routes for the synthesis of ethylenediaminetriacetic acid were achieved via its N-benzyl derivative, which was subsequently hydrolyzed in alkaline solutions to ED3ANa.sub.3, thus avoiding cyclization to its 2-oxo-1,4-piperazinediacetic acid (3KP) derivative. Syntheses attempted by both the alkaline condensation of chloroacetic acid with ethylenediamine, and the carboxymethylation of the diamine with formaldehyde and sodium cyanide resulted in complex mixtures requiring complex extraction techniques (e.g. almost exclusive solubility of 3KP in boiling dimethylformamide, Can. J. Chemistry 1970, 48(1), 163-175) to generate the desired product, and then in only relatively poor yield. In addition, conventional processes resulted in large quantities of by-product, such as ethylenediaminetetraacetic acid (ED4A). Where the by-products were especially objectionable, complicated blocking techniques were necessary in order to achieve a relatively pure solution.
One example of the synthesis of ethylenediamine-N,N,N'-triacetic acid is shown in Chemical Abstracts 78, Vol. 71, page 451, no. 18369c, 1969. There it is disclosed that ethylenediamine reacts with ClH.sub.2 CCO.sub.2 H in a 1:3 molar ratio in basic solution at 10.degree. C. for 24 hours to form a mixture from which ethylenediamine-N,N,N'-triacetic acid can be separated by complexing the same with Co(III). The resulting cobalt complexes can be isolated through ion exchange.
These conventional processes do not produce ED3A with sufficient purity or in sufficient quantity to make the preparation of N-acyl derivatives of ED3A economically attractive. Such derivatives are desirable from the technical standpoint in view of their utility as surfactants, corrosion inhibitors, lubricant enhancers, enzyme inhibitors, metal precipitation additives, chelants, emulsifiers, etc.
Co-pending U.S. Pat. No. 5,250,728, the disclosure of which is hereby incorporated by reference, discloses a simple process for the synthesis of ED3A or its salts in high yield. Specifically, a salt of N,N'-ethylenediaminediacetic acid (ED2AH.sub.2) is condensed with stoichiometric amounts, preferably slight molar excesses of, formaldehyde, at temperature between 0.degree. and 110.degree. C., preferably 0.degree. to 65.degree. C. and pH's greater than 7.0 to form a stable 5-membered ring intermediate. The addition of a cyanide source, such as gaseous or liquid hydrogen cyanide, aqueous solutions of hydrogen cyanide or alkali metal cyanide, in stoichiometric amounts or in a slight molar excess, across this cyclic material at temperatures between 0.degree. and 110.degree. C., preferably between 0.degree. and 65.degree. C., forms ethylenediamine N,N'-diacetic acid-N'-cyanomethyl or salts thereof (mononitrile-diacid). The nitrile in aqueous solutions may be spontaneously cyclized in the presence of less than 3.0 moles base: mole ED2AH.sub.2, the base including alkali metal or alkaline earth metal hydroxides, to form 2-oxo-1,4-piperazinediacetic acid (3KP) or salts thereof, which is the desired cyclic intermediate. In the presence of excess base, salts of ED3A are formed in excellent yield and purity. This U.S. Pat. No. 5,250,728 also discloses an alternative embodiment in which the starting material is ED2AH.sub.a X.sub.b, where X is a base cation, e.g., an alkali or alkaline earth metal, a is 1 to 2, and b is 0 to 1 in aqueous solutions. The reaction mixture also can be acidified to ensure complete formation of carboxymethyl-2-oxopiperazine (the lactam) prior to the reaction. Formaldehyde is added, essentially resulting in the hydroxymethyl derivative. Upon the addition of a cyanide source, 1-cyanomethyl-4-carboxymethyl-3-ketopiperazine (mononitrile monoacid) or a salt thereof is formed. In place of CH.sub.2 O and a cyanide source, HOCH.sub.2 CN, which is the reaction product of formaldehyde and cyanide, may also be employed in this method. Upon the addition of any suitable base or acid, this material may be hydrolyzed to 3KP. The addition of a base will open this ring structure to form the salt of ED3A.
U.S. Pat. Nos. 5,177,243 and 5,191,081, the disclosures of which are incorporated herein by reference, disclose various intermediates in the aforementioned syntheses.
In view of this relatively new technology, ethylenediaminetriacetic acid now can be readily produced in bulk and high yield.
It is therefore an object of the present invention to produce N-acyl derivatives of ethylenediaminetriacetic acid in high conversions and excellent yield.